Table 1.
Characteristics of included studies
| S. No | Study | Study groups (sample size) | Telomere measurement | Telomere length (Mean ± SD) | Statistical measure and analysis | Variables | Short telomere cut-off | Conclusion |
|---|---|---|---|---|---|---|---|---|
| 1 | Sanchez-Vazquez et al. [10] |
COVID-19 1. Mild (7) 2. Moderate (35) 3. Severe (39) 4. Acute (5) |
q-PCR (relative ratio) TRF HT-Q-FISH |
13.81 ± 1.66 13.97 ± 1.96 12.33 ± 2.82 13.64 ± 0.69 (Data were extracted from Fig. 6A of the original study and the mean ± SD was calculated) |
r − 0.145 (Correlation) | Short telomeres and severity score | < 3 kb | Shorter telomeres are associated with increased severity in COVID-19 patients |
| 2 | Dos Santos et al. [11] |
1. Symptomatic COVID-19 negative (12) 2. COVID-19 positive no hospitalization (15) 3. COVID-19 respiratory dysfunction (17) 4. COVID-19 ICU mechanical ventilation (9) |
q-PCR (relative ratio) |
94.36 ± 51.10 70.80 ± 50.16 35.88 ± 9.624 11.05 ± 3.134 (Data were obtained from the author through private correspondence via email) |
Ref 0.043 0.002 (Ref: no hospitalization) |
Short telomeres and COVID-19respiratory dysfunction (moderate) Short telomeres (< median LTL) and COVID-19 ICUmechanical ventilation (severe) |
Median LTL (38.8 AU) | Shorter LTL is significantly associated with severe COVID-19 infection |
| 3 | Froidure et al. [12] |
Hospitalized COVID-19 patient 1. TL < 10 percentile (28) 2. TL > 10 percentile (42) |
Flow-FISH | – |
OR 3.24 (1.21–8.55) Ref: TL > 10% |
Short telomeres vs. critical disease (ICU/Death) | TL < 10% | Short telomeres are associated with increased risk for ICU admission or mortality, regardless of age in COVID-19 patients |
| 4 | Wang et al. [33] |
1. COVID-19 with hospitalization (5861) 2. COVID-19 without hospitalization (914) |
q-PCR (relative ratio) |
− 0.14 ± 0.97 − 0.03 ± 1.00 (Data were obtained from Table 1 of the original study |
Composite: 1.17 (1.05–1.30) Component: 1.17 (hospitalization) 1.32 (critical care) 1.36 (respiratory support) 1.36 (Death) Ref: (No hospitalization) |
LTL (age adjusted) (per 1 SD shorter) and adverse outcomes | (per 1 SD shorter) | Shorter LTL is independently associated with severe COVID-19 and hospitalization |
| 5 | Alessia Mongelli et al. [31] |
1. COVID-19 free (144) 2. Post-COVID-19 (117) |
q-PCR (absolute) |
10.67 ± 11.69 3.03 ± 2.39 (Data were obtained from Table II of the original study) |
– | – | – | TL shortening is associated with significant acceleration of biological age, mainly in the younger COVID-19 individuals |
| 6 | McGroder et al. [30] |
COVID-19 survivors (4 months post-COVID-19) 1. Normal CT (31) 2. Non-fibrotic (13) 3. Fibrotic (32) |
q-PCR-relative ratio |
1.4738 (0.1798) 1.3748 (0.2164) 1.3714 (0.2812) (Data were obtained from the author through private correspondence via email) |
1.5 (1.06–1.72) Ref: Normal CT (Multivariable logistic regression) |
Age-adjusted Telomere length (per 10% decrease in TL) and fibrotic-like patterns | (per 10% decrease in TL) | Short telomeres are associated with fibrotic Interstitial Lung Abnormalities in COVID-19 survivors |
| 7 | Franzen et al. [29] |
1. COVID-19 with ARDS (12) 2. COVID-19 without ARDS (5) |
Flow-FISH |
5.83 ± 1.80 6.24 ± 1.88 (Data were extracted from Fig. 6A of the original study and the mean ± SD was calculated) |
– | – | – | Shortened telomere length or accelerated epigenetic age is not associated with severe COVID-19 |
| 8 | Benetos et al. [27] |
1. COVID-19 (17) 2. Non-COVID-19 (21) |
TESLA (absolute) SB |
3.42 ± 0.33 3.52 ± 0.39 6.52 ± 0.57 6.64 ± 0.80 (Data were obtained from Supplementary Table 1 of the original study) |
– | – | – | Short telomeres are associated with lower lymphocyte count in COVID-19 older patients |
| 9 | Retuerto et al. [32] |
1. Healthy control group (169) 2. COVID-19 hospitalized cohort (251) WHO OS 3. Hospitalized no oxygen therapy WHO OS 4. Oxygen by mask or nasal prongs WHO OS 5. Non-invasive ventilation or high-flow oxygen WHO OS 6. Intubation and mechanical ventilation WHO OS 7. Ventilation and additional organ support WHO OS 8. Death |
q-PCR-absolute length |
7.1536 ± 0.4719 (non-severe COVID-19-Combined mean ± SD of WHO OS 3 & 4) 4.8677 ± 1.2554 (Severe COVID-19—Combined mean ± SD of WHO OS 5, 6, 7, 8) (Data were extracted from Fig. 2B of the original study and converted to mean ± SD) |
r = − 0.03, p = 0.72 (correlation analysis) p = 0.6 (ANOVA) |
Duration of oxygen therapy (a measure of covid-19 severity) vs age-adjusted TL Either age-adjusted or absolute (Kb) TL was similarly decreased in all the groups by COVID-19 severity scores |
Shorter TL is not associated with COVID-19 clinical outcomes nor with persistent post-COVID-19 manifestations | |
| 10 | Cao et al. [28] |
1. Healthy individuals (232) 2. Non-severe COVID-19 (194) 3. Severe COVID-19 (213) |
DNA methylation-based estimator |
4.8676 ± 1.2554 3.7288 ± 1.092 (Data were extracted from Fig. 1f of the original study and the mean ± SD was calculated) |
p < 0.05 (Distribution of telomere attrition in health, non-severe COVID-19 and severe COVID-19) | DNAm TL attrition and severe COVID-19 patients |
Accelerated epigenetic aging is associated with the risk of SARS-CoV-2 infection and developing severe COVID-19 Severe COVID-19 patients had significant DNAm TL attrition acceleration compared with non-severe COVID-19 patients |
|
| 11 | Jiang et al. [14] |
1. Symptomatic Hospitalized COVID-19 patients (9,986) 2. Population controls (1,877,672) (European-ancestry participants) |
q-PCR-relative ratio | NR | OR 0.85 (0.70 to 1.03) | OR of COVID-19 outcomes per-standard deviation (SD) increase in genetically predicted LTL (IVW meta-analysis) | Per SD increase | Genetic evidence does not support shorter LTL as a causal risk factor for COVID-19 susceptibility or severity |
| 12 | Xu et al. [15] |
1. COVID-19 patients with severe symptoms (5,101) 2. Control including individuals without severe COVID-19/without COVID-19 (1,383,241) |
NR | NR |
OR 0.97 (0.66 to 1.42) OR − 0.01 (− 0.02 to − 0.001) |
Odds of severe COVID-19 with short TL Odds of telomere shortening due to severe COVID-19 (IVW meta-analysis) |
NR |
No causal relationship between telomere length and COVID-19 severity Severe COVID-19 could lead to accelerated telomere wear and shorter telomere lengths |
| 13 | Huang et al. [13] |
1. Critically ill COVID-19 (1,388,342) 2. LTL (4,721,74) |
NR | NR | OR 1.00 (0.79–1.28) | Odds of critically ill COVID-19 with LTL (IVW meta-analysis) | NR | LTL was not causally related to critically ill COVID‐19 |
ARDS acute respiratory distress syndrome, AU arbitrary unit, FISH fluorescence in situ hybridization, HT-Q-FISH high-throughput quantitative fluorescence in situ hybridization, ICU intensive care unit, IVW inverse-variance weighted, LTL leukocyte telomere length, NR not reported, OR odds ratio, q-PCR quantitative polymerase chain reaction, sTL shorter telomere length, SD standard deviation, SB southern blotting, TL telomere length, TRF telomere restriction fragment, TeSLA telomere shortest length assay, kb kilobasepairs, Ref reference, WHO OS World Health Organization ordinal scale